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Pharmacoepidemiologic detection of calcium channel blocker‐induced change on digoxin clearance using multiple trough screen analysis
Author(s) -
Suematsu Fumihiro,
Yukawa Eiji,
Yukawa Miho,
Minemoto Masao,
Ohdo Shigehiro,
Higuchi Shun,
Goto Yoshinobu
Publication year - 2002
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.306
Subject(s) - digoxin , concomitant , diltiazem , verapamil , medicine , calcium channel blocker , nifedipine , calcium channel , heart failure , spironolactone , calcium , pharmacology
Nonlinear mixed effects modeling was used to estimate the effects of digoxin–calcium channel blockers (verapamil, diltiazem, nifedipine) in 336 serum levels gathered from 172 patients (104 male and 68 female) receiving oral digoxin as hospital in‐patients. The final model describing digoxin clearance (CL) was CL (l/day)=(87.9+2.71 C cr )0.872 CCB 0.880 CHF 0.937 SPI 0.854 DFAC , where C cr is the estimated creatinine clearance (ml/min); CCB=1 for concomitant administration of calcium channel blockers and CCB=zero otherwise; CHF=1 for the patients with congestive heart failure and CHF=zero otherwise; SPI=1 for concomitant administration of spironolactone and SPI=zero otherwise; DFAC=1 for administration of a half‐tablet of digoxin and DFAC=zero otherwise. Concomitant administration of calcium channel blockers resulted in a 13% decrease in digoxin relative clearance. Copyright © 2002 John Wiley & Sons, Ltd.